α-multistriatin: The first total synthesis of a natural product via antibody catalysis

Article abstract of DOI:10.1002/ijch.199600025

The relevance of antibody catalysis to synthetic organic chemistry is demonstrated here by an efficient total synthesis of (-)-α-multistriatin, the aggregation pheromone of the European elm bark beetle, Scolytus multistriatus, which is the principal vector of the Dutch elm disease, responsible for the severe devastation of the elm population in Europe and North America. The key step in our synthesis of this natural product is an antibody-catalyzed, enantioselective protonolysis of an enol ether to produce a branched ketone. The latter is obtained with an (S) configuration in greater than 99% enantiomeric excess. Catalysis follows Michaelis-Menten kinetics (K_m = 230 μM, k_cat = 0.36 min^-1) and useful rate enhancement (k_cat/k_un = 65,000 at pH 6.5). This abzymic step is followed by twelve chemical steps, with all four asymmetric centers originating from the chirality achieved in the antibody-catalyzed reaction. That specific step is a unique example of a chemical transformation which is difficult to achieve either by an available synthetic methodology or via catalysis with a known enzyme. The synthetic pheromone has been checked in field experiments and found as active as the naturally occurring compound in attracting the European elm bark beetles.